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Health Literacy and Capecitabine Adherence in a Remote Monitoring Pilot Trial for Breast Cancer: Post Hoc Exploratory Analysis.

BACKGROUND: Oral anticancer therapy enables convenient, home-based cancer care but can introduce adherence challenges, particularly with complex dosing schedules. Capecitabine is commonly used in breast cancer, often as adjuvant therapy or in advanced disease, and typically requires twice-daily dosing on cyclical schedules, increasing the risk of missed or incorrect doses. Low health literacy may exacerbate these difficulties, and emerging remote monitoring tools may help close this gap. OBJECTIVE: In this post hoc exploratory analysis, we evaluated whether health literacy (1) was associated with capecitabine adherence and (2) modified a remote monitoring intervention's effectiveness. METHODS: We conducted post hoc analyses of a 2-arm pilot trial that randomized women with breast cancer treated with capecitabine to enhanced usual care (EUC) or remote patient monitoring (RPM). Adherence was captured with a smart pill bottle, Nomi by SMRxT, that recorded dose timing and quantity. Participants in the RPM group received messages for missed or incorrect doses and weekly symptom assessments. Incorrect or missed doses and severe symptoms triggered alerts to the oncologist. Health literacy was assessed at enrollment. To evaluate moderation, we used linear regression with an interaction term (health literacy × intervention arm) predicting adherence (proportion of days). Marginal effects quantified differences in adherence by study arm and health literacy. RESULTS: Among 28 participants (EUC, n=15 and RPM, n=13), 9 (32.1%) had lower health literacy, 16 (57.1%) identified as Black, 10 (35.7%) identified as White, and 15 (53.6%) had income below 200% of the federal poverty level. In the regression model, the health literacy × randomized group interaction did not reach statistical significance (-16.3 percentage points, 95% CI -35.5 to 2.9; P=.09). Predicted adherence among lower health literacy participants was 87.5% in the RPM group and 65.5% in the EUC group (difference: +22.1 percentage points, 95% CI 6.2-37.9; P=.008). Among participants with higher health literacy, adherence was 89.9% in the RPM group and 84.1% in the EUC group (difference: +5.7 percentage points, 95% CI -5.2 to 16.7; P=.29). Within the EUC group, predicted adherence was 18.6 percentage points lower among those with lower versus higher health literacy (95% CI -32.4 to -4.9; P=.01); within the RPM group, this difference was 2.3 percentage points lower among those with lower versus higher health literacy (95% CI -15.8 to 11.1; P=.73). CONCLUSIONS: In this post hoc exploratory analysis, the estimated difference in capecitabine adherence between the RPM and EUC groups was larger among participants with lower health literacy. Although the formal interaction test was not statistically significant, the magnitude and direction of the observed difference support further investigation of RPM as a potential approach to improve adherence among patients facing health literacy-related adherence barriers. Larger, prospectively powered studies are needed to confirm these findings and evaluate downstream clinical outcomes.

Humans

Remotely Supervised, Home-Based Transcranial Direct Current Stimulation for Major Depressive Disorder: Systematic Review and Meta-Analysis.

BACKGROUND: Major depressive disorder affects over 280 million people worldwide, and access to effective treatment remains limited. Transcranial direct current stimulation (tDCS) is a noninvasive option, and portable devices now allow for home-based delivery under varying degrees of remote supervision. OBJECTIVE: This study aimed to systematically review and meta-analyze the efficacy, safety, feasibility, and acceptability of home-based and remotely supervised tDCS for depressive disorders. METHODS: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 and PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta-Analyses literature search extension) guidelines, we searched MEDLINE, Embase, Web of Science, the Cochrane databases, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform up to July 2025, with backward and forward citation searching. Two reviewers independently screened records, extracted data, and assessed risk of bias (version 2 of the Cochrane risk-of-bias tool for randomized trials, Newcastle-Ottawa Scale for observational studies, and Critical Appraisal Skills Programme for qualitative studies) and certainty of evidence (Grading of Recommendations Assessment, Development, and Evaluation; GRADE). RESULTS: This review included 12 distinct studies (16 reports), of which 6 (50%) were randomized sham-controlled trials forming the meta-analytic pool. Active home-based tDCS produced a small, statistically significant improvement over sham (pooled Hedges g=0.36, 95% CI 0.06-0.66; P=.03; I2=34.3%). The effect was not robust to removal of the single largest positive trial (omitting the one study from 2025: g=0.39, 95% CI -0.12 to 0.91), and trial-level results were mixed: the 2 largest trials (one unsupervised [n=210] and one self-administered [n=141]) were negative on their primary depression outcomes, whereas the largest real-time supervised trial (n=174) was positive (between-group 95% CI 0.51-4.01; P=.01). This estimate was concordant in direction with an independent peer-reviewed meta-analysis of overlapping trials, which reported a pooled Montgomery-Åsberg Depression Rating Scale reduction (weighted mean difference -2.74, 95% CI -4.19 to -1.29) and Hamilton Depression Rating Scale reduction (weighted mean difference -2.24, 95% CI -4.16 to -1.49), attenuating to nonsignificance (P>.05) in major depressive disorder without comorbid cognitive impairment. The pooled effect fell at or near the minimal clinically important difference. GRADE certainty was moderate. Adverse events were predominantly mild: one pilot study was terminated early for skin lesions, and one nonfatal suicide attempt occurred in an unsupervised trial. CONCLUSIONS: Home-based and remotely supervised tDCS produces a small, statistically significant but clinically modest antidepressant effect that is sensitive to the inclusion of the largest positive trial, with the 2 largest trials being negative. The available controlled evidence does not establish supervision intensity as a determinant of efficacy. Current data are insufficient to recommend routine clinical adoption; adequately powered trials with standardized supervision and longer follow-up are needed.

Humans

User Engagement and Feature Preferences in an AI-Powered mHealth Intervention for Diabetes Prevention: Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND: Prediabetes is highly prevalent and increasing globally, yet lifestyle interventions remain underused. AI-driven mobile health (mHealth) tools can help scale diabetes prevention efforts, but the key factors driving their success are not well understood. OBJECTIVE: This post hoc secondary analysis of a randomized controlled trial (RCT) aimed to characterize the most valued features and the role of user engagement in outcomes of a fully automated mHealth intervention for diabetes prevention. METHODS: Data from 151 participants with prediabetes and overweight or obesity who were assigned to an AI-based diabetes prevention program (Sweetch) in a parent RCT (NCT05056376) were analyzed. Engagement (defined as the total number of days the app was used) was categorized into tertiles (low, medium, and high). Baseline characteristics were compared across engagement groups using ANOVA, Kruskal-Wallis, and chi-square tests, and regression models assessed the association between engagement and achievement of diabetes risk reduction outcomes (&#x2265;5% weight loss, &#x2265;4% weight loss with &#x2265;150 min/week of physical activity, or &#x2265;0.2 percentage point reduction in hemoglobin A1c [HbA1c] at 12 months). Perceived usefulness of intervention features was surveyed at 12 months. RESULTS: Median engagement was 98 (IQR 34-232) days. Older age (P<.001) and lower baseline BMI (P=.04) were significantly associated with higher engagement. Compared with low engagement, high engagement was associated with greater odds of achieving the composite diabetes risk reduction outcome (odds ratio [OR] 2.59, 95% CI 1.11-6.01; P=.03), &#x2265;5% weight loss (OR 3.31, 95% CI 1.16-9.42; P=.03), and &#x2265;0.2 percentage point reduction in HbA1c (OR 3.57, 95% CI 1.19-10.75; P=.02). Participants most frequently rated weight tracking, physical activity tracking, and the digital body weight scale as the features that were most helpful for achieving their health goals. CONCLUSIONS: Higher engagement with an AI-driven intervention requiring no human intervention was associated with improved diabetes risk reduction. Contrary to concerns about lower digital literacy, older adults engaged with the intervention more than younger adults. Features related to weight and physical activity tracking were most valued by patients in the program. TRIAL REGISTRATION: ClinicalTrials.gov NCT05056376; https://clinicaltrials.gov/study/NCT05056376.

Humans

Digital Mindfulness Intervention for Pregnant Women With Affective Disorders and Acute Stress Reactions: Prespecified Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND: Pregnant women with ICD-10 (International Statistical Classification of Diseases, Tenth Revision) affective or stress-related disorders face an elevated risk of perinatal depression and anxiety, yet evidence on digital nonpharmacologic interventions for this population remains limited. OBJECTIVE: This study evaluated the effectiveness of an 8-week digital mindfulness-based intervention (eMBI) compared with treatment as usual (TAU) among pregnant women with ICD-10 affective or stress-related disorders participating in a randomized controlled trial (RCT). METHODS: This prespecified secondary analysis was conducted within a multicenter RCT in Baden-W&#xfc;rttemberg, Germany. Pregnant women aged 18 years and older with elevated depressive symptoms (Edinburgh Postnatal Depression Scale [EPDS]>9) and ICD-10-diagnosed affective or stress-related disorders were randomized 1:1 to eMBI or TAU. The intervention consisted of 8 weekly app-based mindfulness sessions (45 min each) delivered during gestational weeks 29-36, with no direct therapist contact. The primary outcome was continuous depressive symptom severity measured with the EPDS at 4-6 weeks post partum. Secondary outcomes included the EPDS at 6 months post partum, generalized anxiety (State-Trait Anxiety Inventory-State [STAI-S], State-Trait Anxiety Inventory-Trait [STAI-T]), and Pregnancy-Related Anxiety Questionnaire-Revised (PRAQ-R). Analyses followed the intention-to-treat (ITT) principle, using mixed models for repeated measures and multiple imputation. RESULTS: Of the 5299 screened women, 147 met the inclusion criteria for this subgroup analysis (intervention group [IG] had n=73 women and control group had n=74 women). Groups were comparable at baseline. The IG showed significantly greater reductions in EPDS scores at gestational week 34 (&#x394;=-2.21, P=.01), week 36 (&#x394;=-3.25, P=.01), and 4-6 weeks post partum (&#x394;=-4.81, P=.007). Treatment effects remained robust under conservative missing-data assumptions. At 4-6 weeks post partum, a higher proportion of participants in the IG achieved clinically meaningful improvement (31/73, 42.5% vs 21/74, 28.4%; adjusted odds ratio 1.56, 95% CI 1.19-2.05; P=.001). Anxiety outcomes followed a similar pattern, whereas pregnancy-related anxiety did not differ between groups. CONCLUSIONS: In this prespecified subgroup of pregnant women with ICD-10 affective or stress-related disorders, the eMBI was associated with clinically meaningful reductions in depressive symptoms from late pregnancy to 4-6 weeks post partum. Effects at 6 months post partum were attenuated and less stable across missing-data assumptions. These findings support eMBIs as a scalable, nonpharmacological adjunct to perinatal mental health care for women with affective or stress-related disorders, while confirmation in adequately powered trials with strategies to reduce postpartum attrition is warranted.

Humans

Transcranial Magnetic Stimulation for Patients with Exposure Therapy Resistant Obsessive-Compulsive Disorder (TETRO): Study Protocol for a Multicenter Randomized Controlled Trial.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a disabling mental disorder, characterized by obsessions, compulsions, and substantial morbidity. Approximately 50% of adults with OCD fail to achieve satisfactory outcomes from first-line treatments, such as exposure therapy with response prevention (ERP), with or without medication. This leads to chronic social, educational, and occupational impairment. While invasive procedures such as deep brain stimulation are available for severe, treatment-refractory cases, a need remains for less invasive alternatives. Repetitive transcranial magnetic stimulation (rTMS), a noninvasive intervention, shows promise in reducing OCD symptoms. Unlike in depression, rTMS is not yet reimbursed for OCD in the Dutch healthcare system. OBJECTIVE: This study examines the efficacy and cost-effectiveness of low-frequency (1Hz) rTMS targeting the presupplementary motor area (pre-SMA) compared to sham rTMS as an adjuvant treatment to ERP in adults with OCD with inadequate response to first-line treatment. METHODS: A total of 250 adults with OCD will be enrolled in this multicenter randomized controlled trial. Participants will be randomly assigned to ERP combined with either active or sham 1Hz rTMS over the pre-SMA. Treatment is administered 4 times weekly for at least 5 weeks (20 rTMS-ERP sessions), with optional extension of 1 to 2 weeks, up to 28 rTMS-ERP sessions. Clinical assessments occur at baseline, weekly during treatment, posttreatment, and at 3, 6, and 12 months follow-up. Participants undergo pre- and posttreatment (functional) (MRI) scans, including a symptom provocation task. Blood sampling takes place pre- and posttreatment and at 3-month follow-up. The primary outcome is OCD severity at posttreatment, as measured by the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Secondary outcomes include functional improvement, quality of life, and societal costs. Pretreatment symptom profiles, genotype, and brain network topology will be analyzed as predictors of response and relapse risk. Pre-to-post treatment change in blood-based and magnetic resonance (MR)-based neuroplasticity markers will help explore differential mechanisms between ERP alone and combined rTMS-ERP. We expect that the verum rTMS protocol will be cost-effective compared to sham-rTMS. RESULTS: Recruitment started in April 2022, and as of February 2026, 201 participants have been enrolled. Posttreatment assessments are projected to be completed in December 2026, with final one-year follow-up evaluations anticipated by the end of 2027. CONCLUSIONS: To our knowledge, this study is the first adequately powered randomized controlled trial examining efficacy, cost-effectiveness, and mechanism of action of rTMS for OCD as adjuvant therapy to ERP. In case of efficacy and/or cost-effectiveness, it will pave the way for rTMS as insured health care for adults with OCD in the Netherlands, and possibly other European countries. Furthermore, this trial will provide insight into the mechanisms of treatment response to intensive ERP, with and without adjunctive rTMS, as well as potential side effects, individual variability, and long-term outcomes in adults with OCD.

Humans

Comparative Efficacy of Different AI Systems for Polyp Detection by Size During Colonoscopy: Systematic Review and Network Meta-Analysis.

BACKGROUND: Colorectal cancer remains a leading cause of death despite being largely preventable through polypectomy. AI systems designed to enhance polyp detection during colonoscopy have shown promise, but the extent to which they improve detection of different-sized polyps remains unclear. OBJECTIVE: This study compared the size-stratified efficacy of AI-assisted colonoscopy vs standard colonoscopy using the Hartung-Knapp-Sidik-Jonkman (HKSJ) method, and generated exploratory rankings while acknowledging all cross-platform comparisons are indirect. METHODS: This systematic review and network meta-analysis (NMA) searched PubMed, Embase, Cochrane CENTRAL, and Web of Science from inception to July 25, 2026, supplemented by citation searching. We included randomized controlled trials (RCTs) comparing AI-assisted vs standard colonoscopy in adults (&#x2265;18 years of age), reporting mean polyp detection counts stratified by size (&#x2264;5 mm, 6-9 mm, and &#x2265;10 mm). Two reviewers screened studies, extracted data, and assessed risk of bias using the Cochrane Risk of Bias 2.0. We conducted frequentist NMA using the HKSJ method with restricted maximum likelihood estimation, calculated 95% prediction intervals (PIs), and assessed heterogeneity using I2 and &#x3c4;2. Certainty of evidence was rated using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework. RESULTS: A total of 13 RCTs (4156 participants) compared 8 AI systems to standard colonoscopy, forming a network without direct AI comparisons. For diminutive polyps (&#x2264;5 mm), AI showed a modest advantage (standardized mean difference [SMD] 0.21, 95% CI 0.07 to 0.35, 95% PI -1.12 to 1.54), but substantial heterogeneity (I2=86.6%) and wide PI crossing the null indicated high uncertainty. EndoScreener showed the most consistent evidence (SMD 0.36, 95% CI 0.18-0.54). For small and large polyps, effects were minimal (SMD 0.02, 95% CI -0.02 to 0.06, 95% PI -0.03 to 0.07; SMD 0.01, 95% CI 0.00-0.02, 95% PI -0.01 to 0.03). GRADE certainty was very low for diminutive polyps and low for small and large polyps. Sensitivity analysis excluding Tianjin YuJin did not materially change findings. CONCLUSIONS: AI may modestly enhance diminutive polyp detection, but effects on small and large polyps are minimal, with no platform superiority. Given very low to low certainty, findings are hypothesis-generating. This exploratory NMA provides size-stratified comparisons that can inform future head-to-head trial design. Unlike prior reviews aggregating all polyp sizes, we show the overall AI benefit is driven by diminutive polyp detection, providing a framework for targeted deployment-prioritizing AI for diminutive polyp screening, with limited value for larger lesions. Head-to-head trials are urgently needed. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD420251266932; https://www.crd.york.ac.uk/PROSPERO/view/CRD420251266932.

Colonoscopy

The Impact of Chatbot Type and Normative Messaging on Chatbot Usage Intention Based on the Health Technology Acceptance Model: Randomized Controlled Trial.

BACKGROUND: Digital health tools, such as health chatbots, may improve access to scalable health support, but adoption remains inconsistent. Existing models do not fully integrate technology acceptance factors with health motivation factors relevant to digital health use. OBJECTIVE: This study proposed and tested the health technology acceptance model and examined whether normative message framing and chatbot type were associated with health motivation, technology acceptance, and intention to use a health chatbot. METHODS: In October 2025, we conducted a 4 &#xd7; 2 between-participants online experiment with 1000 US adults recruited from a nationally representative YouGov panel. Participants were randomized to 1 of 8 conditions varying norm message type (self-oriented, peer-oriented, expert-oriented, or family-oriented) and chatbot type (AI-powered or rule-based) in a cancer prevention and genetic risk information scenario. Outcomes included descriptive norms, injunctive norms, perceived susceptibility, perceived severity, perceived benefits, self-efficacy, perceived ease of use, trust, privacy concerns, and usage intention. Data were analyzed using a multivariate ANOVA with Bonferroni-adjusted post hoc tests and multiple linear regression. RESULTS: Peer-oriented and family-oriented messages produced higher usage intention than expert-oriented messages, and peer-oriented messages also increased descriptive norms, injunctive norms, self-efficacy, and trust. AI-powered chatbots were associated with higher usage intention (P=.02) and greater trust (P=.008) than rule-based chatbots. In regression analyses, the model explained 50.8% of the variance in usage intention. Usage intention was positively associated with descriptive norms (&#x3b2;=0.087; P=.003), injunctive norms (&#x3b2;=0.078; P=.009), perceived susceptibility (&#x3b2;=0.051; P=.03), perceived benefits (&#x3b2;=0.253; P<.001), and trust (&#x3b2;=0.33; P<.001), and negatively associated with perceived severity (&#x3b2;=-0.047; P=.049) and privacy concerns (&#x3b2;=-0.11; P<.001). Perceived ease of use and self-efficacy were not significant predictors. CONCLUSIONS: The health technology acceptance model was a useful framework for explaining the intention to use a health chatbot by combining technology acceptance and health motivation constructs. Both social design features and chatbot design features shaped adoption-related beliefs, with peer-oriented and family-oriented framing and AI-powered chatbots showing particular promise. Trust and privacy concerns remained central determinants of intended use.

Humans

Multidisciplinary mHealth Rehabilitation for Patients With Abdominal Cancer Who Are Receiving Chemoradiotherapy: Randomized Phase II Trial.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) for abdominal cancer frequently induces muscle loss, weight loss, and malnutrition. OBJECTIVE: This exploratory randomized phase II trial evaluated whether a multidisciplinary, mobile health (mHealth)-based multimodal rehabilitation program could preserve handgrip strength and muscle mass in patients with abdominal cancer undergoing CCRT. METHODS: In this prospective, multicenter, randomized, open-label phase II trial (NCT05325554), 111 eligible patients with abdominal malignancies scheduled for CCRT were randomly assigned (1:1) to receive either multidisciplinary mHealth rehabilitation care (MRC; n=57) or standard care (SC; n=54). The MRC program was delivered by a dedicated multidisciplinary team using the AiNST mHealth platform and wearable heart rate monitors. The primary end point was handgrip strength at the end of CCRT (analyzed with analysis of covariance adjusting for baseline). Secondary end points were exploratory and analyzed without multiplicity adjustment; sensitivity analysis using false discovery rate (FDR) correction was performed. RESULTS: Between February 2022 and April 2023, 111 patients were enrolled. Adherence was high (n=93, 83.9% achieved exercise targets). After adjusting for baseline handgrip strength, the MRC group had significantly higher handgrip strength at the end of CCRT than the SC group (adjusted mean difference 4.87 kg, 95% CI 3.36-6.38; P<.001). Exploratory analyses of secondary end points (without multiplicity adjustment) showed that the MRC group also had better preservation of body weight (P=.005), skeletal muscle mass (P<.001), serum albumin (P=.009), prealbumin (P=.02), and lower rates of hematological toxicity (P<.05), as well as improved psychological status (distress thermometer [DT] and Hospital Anxiety and Depression Scale [HADS]) and nutritional scores (Nutritional Risk Screening 2002 [NRS-2002] and Patient-Generated Subjective Global Assessment [PG-SGA]) at the end of CCRT (all P<.05). All nominally significant secondary end points remained significant after FDR correction (q<.05). These findings are preliminary and should be interpreted with caution due to the open-label design, population heterogeneity, and exploratory secondary analyses. CONCLUSIONS: In this exploratory phase II trial, a multidisciplinary, mHealth-based multimodal rehabilitation program was associated with better preservation of handgrip strength, muscle mass, and nutritional status, as well as lower rates of certain treatment toxicities, compared with SC. However, definitive conclusions are limited by the open-label design, heterogeneity of tumor types, and short follow-up. Larger, blinded phase III trials are needed to confirm these findings.

Humans

Genome-wide association study of estimated glomerular filtration rate using repeated measurements in the Taiwan Biobank.

BACKGROUND: Chronic kidney disease (CKD) is a major global public health issue, with genetic factors playing a significant role in kidney function. Although genome-wide association studies (GWAS) have identified numerous loci associated with estimated glomerular filtration rate (eGFR), most studies relied on a single time-point measurement, which limits the capacity to account for within-individual measurement variability. METHODS: We performed a repeated-measurement GWAS in the prospective Taiwan Biobank (Taiwanese ancestry; n = 25,004) using two repeated creatinine-based eGFR measurements. Repeated eGFR values were analyzed using a linear mixed-effects model with a subject-specific random intercept and time-varying covariates, providing a more precise estimate of eGFR level. Identified loci underwent functional annotation (expression quantitative trait locus, deleteriousness prediction, and epigenetic markers) and were compared with results from a single-measurement GWAS. RESULTS: Six loci associated with eGFR were identified, including four previously reported regions (1q22, 4q21.1, 11p14.1, and 17q21.2) and two additional loci (6p21.32 and 15q24.2). Functional annotation implicated several candidate genes-such as MUC1/EFNA1, SHROOM3, HLA-DQB1, MPPED2, NRG4, and PGAP3/FBXL20-in the regulation of kidney function. CONCLUSION: Incorporating repeated eGFR measurements into GWAS may improve phenotypic precision for identifying genetic associations with kidney function. This study identified eGFR-associated loci and biologically plausible candidate genes in a Taiwanese population, which require further replication and functional validation.

Chronic kidney disease

The role of particle therapy in the treatment of locally recurrent rectal cancer: a systematic review.

BACKGROUND: Colorectal cancer is a common malignancy. Advancements in multimodality treatment have improved outcomes. About 2-10% of patients will have a local recurrence even after optimal treatment. Salvage surgical treatment is the treatment of choice, however, in posterior and lateral recurrences, surgery is linked to a high rate of treatment-related morbidity. Some recurrences remain unresectable even after neoadjuvant treatment. MATERIALS AND METHODS: A systematic literature review was performed to search for studies on curative-intent radiation therapy (RT) with photons, stereotactic body radiation therapy (SBRT) and particle beam therapy. The aim of the literature search was to define the role of particle therapy in the treatment of patients with unresectable or inoperable local recurrences of rectal cancer where neoadjuvant treatment is unlikely to result in downstaging, leaving patients with RT as the only curative treatment option. RESULTS: 32 studies which fulfil the criteria were identified. In general, SBRT and particle beam therapy permitted the application of significantly higher doses to the target without a concomitant increase in treatment-related toxicities. CONCLUSIONS: For unresectable and inoperable locally recurrent rectal cancer ablative radiotherapy techniques such as SBRT and particle beam therapy offer a curative treatment approach as an alternative to surgery. SBRT can be offered for small local and nodal recurrences, while particle beam therapy can be offered for larger recurrences and complex shapes spanning several anatomical compartments as well. Further research is needed to stratify patients according to their need and eligibility for the different possible modalities of curative-intent RT.

Humans

The effect of drysuit diving in warm water on body temperature and post immersion orthostatic hypotension.

INTRODUCTION: Warm-water diving can limit heat dissipation, particularly when performed in fully encapsulating protective gear, leading to substantial thermal and cardiovascular strain that may impair diver safety. Following immersion, removal of hydrostatic support combined with heat-induced vasodilation may reduce central blood volume and increase susceptibility to orthostatic intolerance during egress and recovery. The extent to which this thermal strain impairs post-immersion orthostatic tolerance remains unknown. METHODS: Four randomised, crossover immersion trials were conducted at 28&#xb0;C, 33&#xb0;C, 38&#xb0;C without precooling (38&#xb0;C), and 38&#xb0;C with precooling (38&#xb0;C + Cool), with subjects wearing fully encapsulating dive gear. Subjects walked for up to 60 minutes at approximately 50% of O2max heart rate (HR) or until core temperature (Tc) reached 38.5&#xb0;C, or they voluntarily stopped. Tc, HR, and perceptual measures were recorded every 10 minutes. Orthostatic tolerance was assessed after immersion via a 70&#xb0; head-up tilt test. RESULTS: Eight healthy adults completed all aspects of the study. Tc and HR were higher during both 38&#xb0;C conditions compared with 28&#xb0;C and 33&#xb0;C (all P < 0.01) with no differences between 38&#xb0;C and 38&#xb0;C + Cool. Sweat loss exceeded 1.2 (SD 0.67) L&#x22c5;h-1 in both 38&#xb0;C conditions compared with &#x2264; 0.3 (0.32) L&#x22c5;h-1 at 28&#xb0;C and 33&#xb0;C (P < 0.01). Survival analysis showed orthostatic tolerance decreased with increasing thermal stress (log-rank P = 0.027; trend P = 0.003). Precooling did not reduce peak Tc or HR, nor did it improve tolerance time in 38&#xb0;C water. CONCLUSIONS: Encapsulated warm-water diving causes heat stress and cardiovascular strain that persists after immersion, impairing orthostatic tolerance. Precooling does not significantly reduce these outcomes.

Humans

Surgical management of jugular foramen meningiomas: a function-prioritized perioperative workflow.

OBJECTIVE: Jugular foramen meningiomas are challenging because of their deep, neurovascularly crowded location and multicompartment extension; hyperostosis and rigid dural attachment further narrow the corridor and increase the risk of lower cranial nerve morbidity, causing dysphagia and airway complications that may rarely require tracheostomy. This study aimed to describe a contemporary function-first workflow integrating compartment-based anatomy, venous sinus status, preoperative embolization, and continuous vagus nerve monitoring and its relation to clinically actionable recovery endpoints. METHODS: The authors retrospectively reviewed 26 consecutive patients who underwent primary surgery for jugular foramen meningiomas (2014-2025). Tumors were classified as intradural + intrajugular (IJ) or intradural + intrajugular + extracranial extension (IJE). Retrosigmoid, suprajugular, or transjugular approaches were selected by tumor extension and sigmoid-jugular venous status. Selective embolization and continuous vagus nerve monitoring were used when feasible. Outcomes included extubation timing, time to oral intake, 1-year swallowing/voice severity, extent of resection, and salvage stereotactic radiosurgery (SRS) for progression/regrowth. RESULTS: Twenty tumors were IJ and 6 were IJE. Selective embolization was performed in 16 patients (62%) without complications. Continuous vagus nerve monitoring was implemented in 16 patients (62%); lower preservation rates showed an exploratory association with worse 1-year swallowing. All patients were extubated immediately after surgery. Oral intake began by postoperative day &#x2264; 7 in 20 patients (77%); only 1 required > 14 days before resuming oral intake. At 1 year, swallowing and hoarseness remained worse in 54% and 46% of patients, respectively, but almost all cases were mild; the same patient had moderate dysphagia/hoarseness, and none required tracheostomy, gastrostomy, long-term tube feeding, or phonosurgery. Simpson grade IV comprised 69% of cases but predominantly reflected intrajugular/extracranial residual rather than persistent intradural disease. No patient without preoperative facial nerve palsy developed new palsy; serviceable hearing was preserved in 70%, and 38% with preoperative nonserviceable hearing improved to serviceable hearing. During a median 55.6-month follow-up, 3 patients (12%) underwent salvage SRS for regrowth; none required reoperation. CONCLUSIONS: A function-first workflow guided by anatomical compartment extension and intraoperative monitoring can support rapid recovery and durable functional independence in jugular foramen meningiomas. The IJE phenotype identifies a higher-risk subgroup for delayed oral intake and postoperative subjective dysphagia/hoarseness, while continuous vagus nerve monitoring may provide actionable insights to calibrate surgical aggressiveness and support function-prioritized acceptance of intrajugular/extracranial residual with close surveillance and salvage SRS when needed.

Humans

Meningioma methylation profiling as a complement to WHO grading: a single-center experience.

OBJECTIVE: The methylation profile of meningiomas is a promising predictive tool that may improve risk stratification beyond WHO grading. This study aimed to evaluate the clinical relevance and real-world applicability of routine epigenetic testing in meningioma management. METHODS: The authors retrospectively analyzed patients who underwent meningioma resection between January 2021 and December 2023. Histopathological grading (WHO 2021) and methylation profiling (methylation class [MC]) with the MethylationEPIC v1.0 (850k) chip were performed by an independent neuropathologist. RESULTS: A total of 106 patients were included; 81 tumors (76%) were classified as WHO grade 1, 20 (19%) as grade 2, and 5 (5%) as grade 3. Epigenetically, 55 tumors (52%) were classified as benign, 18 (17%) as intermediate, and 2 (2%) as malignant; 31 (29%) could not be classified. Discordances between WHO grading and methylation profiling were observed in 18 of 74 cases. Tumor board decisions were made after a median of 8 days postoperatively, guided by WHO grading; however, the epigenetic report was only available after a median of 23 days. During follow-up, 20 patients experienced tumor progression. Progression was significantly associated with the MC (r = -0.4, p < 0.001) and tumor volume (r = 0.4, p = 0.0005), but not with WHO grading (r = 0.17, p = 0.084). However, the relatively high rate of unclassified tumors and delayed result availability limited the direct impact of MC profiling on immediate clinical decision-making. Interestingly, progression-free survival in MC-unclassified tumors mirrored that of the intermediate group. CONCLUSIONS: Methylation profiling demonstrates superior predictive accuracy for meningioma progression and complements WHO grading, especially in identifying malignant meningiomas. However, its current clinical utility is constrained by technical and logistical limitations. In real-world practice, epigenetic classification should therefore be considered a complementary tool rather than a replacement for established histopathological assessment.

Humans

The use of diode laser and scalpel blade in stage-two dental implant surgery: a comparative study.

OBJECTIVE: The use of lasers in dental implant procedures raises questions regarding the preservation of keratinized tissues and implant outcomes. This study aimed to compare the clinical effects (pain and impression time) and soft tissue healing (keratinization, peri-implant probing, bleeding, and healing) of diode lasers and scalpels used during stage-two dental implant surgery. METHOD AND MATERIALS: A prospective randomized clinical trial with a 1:1 allocation ratio was conducted. The study included 30 patients, each with a single, fully osseointegrated implant. Patients were categorized into two groups. The study group underwent stage-two implant surgery using a 970-nm diode laser. In the control group, implants were exposed using a conventional surgical blade. A comparison between the diode laser and conventional scalpel groups was made based on clinical outcomes (pain and impression time) and soft tissue healing (keratinization, peri-implant probing, bleeding, and healing). Data were analyzed using a paired t test. RESULTS: Pain intensity significantly decreased from immediate postoperative to 7 days in both scalpel (49.87 &#xb1; 6.78, t = 28.48, df = 14, P .001) and diode laser (7.67 &#xb1; 7.58, t = 3.91, df = 14, P = .002) groups. Immediately after surgery, pain scores were significantly higher in the scalpel group compared with the diode laser group (94.53 &#xb1; 4.45 vs 46.93 &#xb1; 5.85, t = 25.076, df = 26.151, P .001). Although pain decreased in both groups by day 7, the scalpel group continued to exhibit significantly greater pain (44.67 &#xb1; 5.96 vs 39.27 &#xb1; 3.73, t = 2.974, df = 23.513, P = .007). Impression time (P = .231) and gingival keratinized tissue (P = .736) did not differ significantly between the scalpel and diode laser approaches. At week 6, the scalpel group exhibited a significantly higher mean peri-implant bleeding index (2.60 &#xb1; 0.507) compared with the laser group (0.07 &#xb1; 0.258, P .001). However, after 12 weeks, no significant difference was observed (1.58 &#xb1; 0.19 vs 1.55 &#xb1; 0.21, P = .748). Laser surgery produced significantly better early wound healing at all intervals (P .001), while intraoperative bleeding was more common with the scalpel technique than with the diode laser (100.0% vs 66.7%, P = .042). CONCLUSION: Compared with the scalpel method, the diode laser method resulted in a significant reduction in pain intensity, improved wound healing, and less peri-implant bleeding during the stage-two dental implant surgery.

Humans

PGR expression as a pharmacogenomic companion biomarker to GENE70-derived genomic risk in ER-positive/HER2-negative breast cancer.

BACKGROUND: The biology of the estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancers is heterogeneous even when they are categorized by their risk via genomics. Transcriptomic PGR expression reflects endocrine pathway activity and may provide complementary biological information within established GENE70-derived genomic-risk categories. Whether this molecular marker improves the biological interpretation of genomic-risk stratification beyond conventional clinicopathological assessment remains uncertain. OBJECTIVES: The aim of this study was to determine whether transcriptomic PGR expression provides complementary biological and prognostic information within reconstructed GENE70-derived genomic-risk categories and refines the characterization of endocrine-related tumour biology in ER-positive/HER2-negative breast cancer. METHODS: This study analysed publicly available transcriptomic and clinical data from three cohorts: METABRIC (discovery cohort), GSE96058/SCAN-B cohort (validation cohort) and TCGA-BRCA cohort (molecular validation cohort). The GENE70-derived genomic-risk score was reconstructed for each cohort using matched genes. Cox regression, Kaplan-Meier analysis and subgroup comparisons were used to assess relationships between PGR expression, clinicopathologic variables, molecular features and survival outcomes. RESULTS: Across the three independent cohorts, low transcriptomic PGR expression was consistently associated with higher GENE70-derived genomic risk, increased MKI67 expression, reduced ESR1 expression and enrichment of the Luminal B subtype. Survival findings differed between cohorts. In the discovery METABRIC cohort, transcriptomic PGR expression showed heterogeneous associations with survival, particularly within GENE70-derived high-risk subgroups, whereas the external GSE96058/SCAN-B validation cohort demonstrated consistent associations between low PGR expression and poorer overall survival in both the overall ER-positive/HER2-negative population and GENE70-derived high-risk subgroups. CONCLUSION: These findings suggest that transcriptomic PGR provides complementary biological and prognostic information within GENE70-derived genomic-risk categories. However, because treatment response was not evaluated in the present study, the findings should not be interpreted as evidence of predictive or pharmacogenomic utility and prospective studies incorporating treatment-response analyses are required before such applications can be established.

Humans

Anti-inflammatory agents after hip and shoulder arthroplasty: A systematic review and meta-analysis.

BACKGROUND: Postoperative inflammation after arthroplasty contributes to pain, delayed mobilization and prolonged hospitalization. Recent randomized trials have evaluated pharmacological anti-inflammatory strategies within contemporary enhanced recovery pathways, but evidence after hip and shoulder arthroplasty remains scattered across different drug classes and perioperative regimens. OBJECTIVES: To synthesize recent randomized controlled trial (RCT) evidence on perioperative anti-inflammatory agents after hip and shoulder arthroplasty. METHODS: PubMed, Embase, Cochrane Library and Web of Science were searched for English-language RCTs published from January 2020 to March 2026. The 2020-2026 window was selected to update evidence generated under modern arthroplasty, anesthesia, multimodal analgesia and enhanced recovery after surgery (ERAS) pathways. Eligible trials included adults undergoing hip or shoulder arthroplasty and compared corticosteroids, cyclooxygenase-2 (COX-2) inhibitors, nonsteroidal anti-inflammatory drug (NSAID)-based/local anti-inflammatory regimens, or related anti-inflammatory interventions with placebo, saline, no treatment, or the same regimen without the target component. Weighted mean differences (WMDs) were pooled using random-effects models. RESULTS: Nine RCTs involving 800 patients were included. Anti-inflammatory interventions significantly reduced postoperative C-reactive protein (CRP) [WMD=-32.18, 95% confidence interval (CI) (-41.16, -23.21), P<0.001], interleukin-6 (IL-6) [WMD=-31.25, 95% CI (-41.79, -20.77), P<0.001], rest pain [WMD=-0.41, 95% CI (-0.58, -0.23), P<0.001], activity pain [WMD=-0.56, 95% CI (-0.83, -0.29), P<0.001] and hospital stay [WMD=-0.54, 95% CI (-0.92, -0.15), P=0.006]. CONCLUSION: Recent RCT evidence suggests that perioperative anti-inflammatory interventions can attenuate early inflammatory responses and improve short-term pain and recovery after hip and shoulder arthroplasty. Because data were limited and clinically heterogeneous, the findings should not be interpreted as evidence favoring a specific drug class, dose, route, or timing.

Humans

[Efficacy and safety of acute-phase transcutaneous auricular vagus nerve stimulation for herpes zoster-related pain in middle-aged and elderly patients with comorbid depression and anxiety].

Objective: To evaluate the efficacy and safety of transcutaneous auricular vagus nerve stimulation (taVNS) during the acute phase in middle-aged and elderly patients with herpes zoster (HZ) comorbid depressive and anxiety states. Methods: This was a randomized controlled trial. Forty middle-aged and elderly patients with acute-phase HZ who attended the Department of Dermatology at Xuanwu Hospital, Capital Medical University, from June 2024 to June 2025 were enrolled and randomly assigned in a 1&#x2236;1 ratio using a random number table to receive either taVNS (n=20) or sham stimulation (n=20) for 5 consecutive days. Both groups received antiviral therapy and on-demand rescue analgesia. Pain, anxiety/depression, and sleep quality were evaluated using the Visual Analog Scale (VAS), the 4-item Patient Health Questionnaire (PHQ-4), and the Insomnia Severity Index (ISI), respectively. The primary outcome was the incidence of subacute pain at 30 days post-rash onset. Secondary outcomes included cumulative analgesic consumption at 1 and 2 weeks after treatment, the changes from baseline (&#x394; values) in PHQ-4 and ISI scores at 2 weeks, and the incidence of postherpetic neuralgia (PHN) at 90 days post-rash onset. Results: In the taVNS group, 7 patients (35%) were female, with a mean age of (64.1&#xb1;9.7) years; in the sham group, 10 patients (50%) were female, with a mean age of (61.5&#xb1;8.5) years. There were no statistically significant differences between the two groups in baseline VAS, PHQ-4, or ISI scores (all P>0.05). The incidence of subacute pain was significantly lower in the taVNS group than in the sham group [5% (1/20) vs 35% (7/20), RD=-30.0% (95%CI:-52.1%--4.9%); RR=0.14 (95%CI: 0.02-1.06); P=0.044]. At 2 weeks after treatment, the &#x394; values of PHQ-4 and ISI in the taVNS group were significantly greater than those in the sham group. The proportion of patients taking Lofentadine and the cumulative Lofentadine consumption at weeks 1 and 2 were both lower in the taVNS group than in the sham group (all P<0.05). No serious adverse events occurred in either group, and the difference in PHN incidence between groups was not statistically significant (P>0.05). Conclusions: Acute-phase taVNS appears to be feasible and safe in middle-aged and elderly patients with HZ and comorbid depressive and anxiety, effectively reducing subacute pain and improving emotional and sleep outcomes.

Humans

[A case of bilateral open-lip schizencephaly with West syndrome due to variant of PAFAH1B1 gene and literature review].

OBJECTIVE: To report the clinical manifestations, genetic features, diagnosis, treatment, and prognosis of a child with bilateral open-lip schizencephaly complicated by West syndrome due to a variant of PAFAH1B1 gene, and review the relevant literature. METHODS: Clinical data of a 4-month-old boy were retrospectively analyzed, and 35 previously reported cases were systematically reviewed. This study was approved by the Medical Ethics Committee of Gansu Provincial People's Hospital (Ethics No.: 2025-871). RESULTS: The 4-month-old boy presented with clustered flexor spasms, hypsarrhythmia on electroencephalography, and developmental regression. Brain magnetic resonance imaging revealed bilateral pachygyria, schizencephaly, and dysgenesis of the corpus callosum. Trio whole-exome sequencing identified a de novo heterozygous NM_000430.4: c.703_704delAG (p.Glu235Metfs*20) frameshift variant in the PAFAH1B1 gene. Sanger sequencing confirmed that neither parent carried this variant. Based on the guidelines from American College of Medical Genetics and Genomics (ACMG), the variant has met the criteria for PVS1+PS2_Moderate+PM2_Supporting, and was classified as pathogenic. After treatment with adrenocorticotropic hormone combined with vigabatrin and other antiseizure medications, the epileptic spasms were controlled and the electroencephalographic abnormalities had improved. However, global developmental delay persisted at the 12-month follow-up. Analysis of the present case and 35 previously reported cases showed that PAFAH1B1-related phenotypes were highly consistent, mainly including infantile spasms (28/36), developmental delay/intellectual disability (29/36), and abnormal brain MRI findings (30/36), predominantly cortical malformations. The reported variant types included deletions, frameshift variants, nonsense variants, missense variants, and splice-site variants. CONCLUSION: PAFAH1B1 gene variants are an important cause for cortical malformations, including schizencephaly, and may lead to secondary West syndrome. This study has systematically summarized the genotypic and phenotypic features of bilateral open-lip schizencephaly complicated by West syndrome associated with a frameshift variant of the PAFAH1B1 gene. For infants with epileptic spasms or early-onset epilepsy accompanied by structural brain abnormalities, early genetic evaluation should be performed, and antiseizure treatment should be integrated with neurodevelopmental rehabilitation to facilitate long-term management.

Humans